Search

Abstract Transthoracic echocardiography (TTE) is widely recognized as one of the principal modalities for diagnosing tricuspid regurgitation (TR). The diagnostic procedures associated with conventional methods are intricate and labor-intensive, with human errors leading to measurement variability, with outcomes critically dependent on the operators’ diagnostic expertise. In this study, we present an innovative assessment methodology for evaluating TR severity utilizing an end-to-end deep learning system. This deep learning system comprises a segmentation model of single cardiac cycle TR continuous wave (CW) Doppler spectra and a classification model of the spectra, trained on the TR CW Doppler spectra from a cohort of 11,654 patients. The efficacy of this intelligent assessment methodology was validated on 1500 internal cases and 573 external cases. The receiver operating characteristic (ROC) curves of the internal validation results indicate that the deep learning system achieved the areas under curve (AUCs) of 0.88, 0.84, and 0.89 for mild, moderate, and severe TR, respectively. The ROC curves of the external validation results demonstrate that the system attained the AUCs of 0.86, 0.79, and 0.87 for mild, moderate, and severe TR, respectively. Our study results confirm the feasibility and efficacy of this novel intelligent assessment method for TR severity.

Abstract Organoids are “mini-organs” that self-organize and differentiate from stem cells under in vitro 3D culture conditions, mimicking the spatial structure and function of tissues in vivo. Extracellular vesicles (EVs) are nanoscale phospholipid bilayer vesicles secreted by living cells, rich in bioactive molecules, with excellent biocompatibility and low immunogenicity. Compared to EVs, organoid-derived EVs (OEVs) exhibit higher yield and enhanced biological functions. Organoids possess stem cell characteristics, and OEVs are capable of delivering active substances, making both highly promising for medical applications. In this review, we provide an overview of the fundamental biological principles of organoids and OEVs, and discuss their current applications in disease treatment. We then focus on the differences between OEVs and traditional EVs. Subsequently, we present methods for the engineering modification of OEVs. Finally, we critically summarize the advantages and challenges of organoids and OEVs. In conclusion, we believe that a deeper understanding of organoids and OEVs will provide innovative solutions to complex diseases. Graphical Abstract

Abstract Background Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 2 diabetes mellitus, and its mechanisms are complex and poorly understood. Despite growing evidence suggesting that ferroptosis plays a significant role in cardiovascular disease, it has been less extensively studied in DCM. Fibroblast growth factor 21 (FGF21), whose mechanism of action is closely related to ferroptosis, is widely utilized in studies focused on the prevention and treatment of glucolipid metabolism-related diseases and cardiovascular diseases. Objective To confirm the significant role of ferroptosis in DCM and to investigate whether FGF21 improves DCM by inhibiting ferroptosis and elucidating its specific molecular mechanisms. Methods The animal DCM models were established through high-fat feeding combined with streptozotocin injection in C57BL/6J mice or by db/db mice, and the diabetic cardiomyocyte injury model was created using high glucose and high fat (HG/HF) culture of primary cardiomyocytes. Intervention modeling of FGF21 were performed by injecting adeno-associated virus 9-FGF21 in mice and transfecting FGF21 siRNA or overexpression plasmid in primary cardiomyocytes. Results The findings indicated that ferroptosis was exacerbated and played a significant role in DCM. The overexpression of FGF21 inhibited ferroptosis and improved cardiac injury and function, whereas the knockdown of FGF21 aggravated ferroptosis and cardiac injury and function in DCM. Furthermore, we discovered that FGF21 inhibited ferroptosis in DCM by directly acting on ferritin and prolonging its half-life. Specifically, FGF21 binded to the heavy and light chains of ferritin, thereby reducing its excessive degradation in the proteasome and lysosomal-autophagy pathways in DCM. Additionally, activating transcription factor 4 (ATF4) served as the upstream regulator of FGF21 in DCM. Conclusions The ATF4-FGF21-ferritin axis mediates the protective effects in DCM through the ferroptosis pathway and represents a potential therapeutic target for DCM.

The recycling and reuse of solid wastes mark the construction industry's development towards sustainable and green technologies. 3D printing technology using recycled solid materials is in great demand for intelligent and low-carbon construction. This paper incorporates crumb rubber (0–1 mm) into the printing ink and analyses the fresh and hardened properties. The results showed that the flowability was positively correlated with rubber ratio but negatively with fiber content. R40F15 (40% rubber and 1.5% fiber) obtained the optimal flowability for 3D printing, which remained above 15 mm for 30min. The compressive strength peaked when incorporating 1.5% fiber, while the flexural strength reached the bottom. X direction generated the highest compressive strength in the whole anisotropic tests, followed by the Y and Z directions. The highest strengths of 1.5% and 2.0% fiber content were 69.45 MPa and 64.5 MPa, incorporating 20% rubber. Thus, surfaces anticipated to bear higher loads in compression should be aligned with the X-axis or, at a minimum, avoid alignment with the Z-axis for optimal structural performance. Y direction obtained the highest flexural strength in all anisotropic tests when incorporating 1.5% fiber. Results from digital image correlation test supported that fiber tended to agglomerate in the Y direction. Besides, the environmental analysis was conducted in this paper to quantitively calculate the impacts of all raw materials to the environment.

Efficient fire response and the coordination of various fire vehicles are paramount for delivering optimal services and conducting effective rescue operations. This study explores the challenges of cooperative station location and vehicle assignment, focusing on the synergistic dispatch of fire vehicles from multiple stations. It highlights that the response time of the last arriving vehicle, crucial for forming a complete and effective response unit, is a critical determinant in the overall success of fire rescue operations. The primary objective of the model is to minimize the total system cost, encompassing both the capital investment in fire stations and the potential losses from fire incidents. By employing a Lagrangian relaxation technique, the model effectively simplifies the optimization challenge into more manageable sub-problems, thereby enhancing solution accuracy. The robustness and flexibility of the model were tested through simulations in a hypothetical network and a real-world scenario, using data from urban fire services. The results demonstrate the model’s scalability and adaptability to different network configurations and operational constraints, showcasing its potential to substantially enhance emergency response efficiency and decision-making in urban fire management. This research makes a significant contribution to emergency response management by providing a validated framework that improves the coordination and effectiveness of fire rescue operations, thereby reducing fire damage and enhancing public safety.

Abstract Metalloproteinases are ubiquitous in organisms. Most metalloproteinases secreted by pathogenic microorganisms are also called virulence factors, because they degrade proteins in the external tissues of the host, thereby reducing the host’s immunity and increasing its susceptibility to disease. Zinc metalloproteinase is one of the most common metalloproteinases. In our report, we studied the biological function of zinc metalloprotease FgM35 in Fusarium graminearum and the pathogen–host interaction during infection. We found that the asexual and sexual reproduction of the deletion mutant ΔFgM35 were affected, as well as the tolerance of F. graminearum to metal stress. In addition, deletion of FgM35 reduced the virulence of F. graminearum. The wheat target TaZnBP was screened using a wheat yeast cDNA library, and the interaction between FgM35 and TaZnBP was verified by HADDOCK molecular docking, yeast two-hybrid, Bi-FC, Luc, and Co-IP assays. The contribution of TaZnBP to plant immunity was also demonstrated. In summary, our work revealed the indispensable role of FgM35 in the reproductive process and the pathogenicity of F. graminearum, and it identified the interaction between FgM35 and TaZnBP as well as the function of TaZnBP. This provides a theoretical basis for further study of the function of metalloproteinases in pathogen–host interactions.

Abstract Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are now recommended for patients with heart failure, but the mechanisms that underlie the protective role of SGLT2i in cardiac remodeling remain unclear. Aldehyde dehydrogenase 2 (ALDH2) effectively prevents cardiac remodeling. Here, the key role of ALDH2 in the efficacy of SGLT2i on cardiac remodeling was studied. Methods Analysis of multiple transcriptomic datasets and two-sample Mendelian randomization were performed to find out the differentially expressed genes between pathological cardiac hypertrophy models (patients) and controls. A pathological cardiac hypertrophy mouse model was established via transverse aortic constriction (TAC) or isoproterenol (ISO). Cardiomyocyte-specific ALDH2 knockout mice (ALDH2CMKO) and littermate control mice (ALDH2flox/flox) were generated to determine the critical role of ALDH2 in the preventive effects of dapagliflozin (DAPA) on cardiac remodeling. RNA sequencing, gene knockdown or overexpression, bisulfite sequencing PCR, and luciferase reporter assays were performed to explore the underlying molecular mechanisms involved. Results Only ALDH2 was differentially expressed when the differentially expressed genes obtained via Mendelian analysis and the differentially expressed genes obtained from the multiple transcriptome datasets were combined. Mendelian analysis revealed that ALDH2 was negatively related to the severity of myocardial hypertrophy in patients. DAPA alleviated cardiac remodeling in mouse hearts subjected to TAC or ISO. ALDH2 expression was reduced, whereas ALDH2 expression was restored by DAPA in hypertrophic hearts. Cardiomyocyte specific ALDH2 knockout abolished the protective role of DAPA in preventing cardiac remodeling. ALDH2 expression and activity were increased in DAPA-treated neonatal rat primary cardiomyocytes (NRCMs), H9C2 cells and AC16 cells. Moreover, DAPA upregulated ALDH2 in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes. Sodium/proton exchanger 1 (NHE1) inhibition contributed to the regulation of ALDH2 by DAPA. DAPA suppressed the production of reactive oxygen species (ROS), downregulated DNA methyltransferase 1 (DNMT1) and subsequently reduced the ALDH2 promoter methylation level. Further studies revealed that DAPA enhanced the binding of nuclear transcription factor Y, subunit A (NFYA) to the promoter region of ALDH2, which was due to the decreased promoter methylation level of ALDH2. Conclusions The upregulation of ALDH2 plays a critical role in the protection of DAPA against cardiac remodeling. DAPA enhances the binding of NFYA to the ALDH2 promoter by reducing the ALDH2 promoter methylation level through NHE1/ROS/DNMT1 pathway. Graphical abstract

Abstract Background Two-line hybrid wheat technology system is one way to harness wheat heterosis both domestically and internationally. Seed vigor is a crucial parameter for assessing seed quality, as enhanced seed vigor can lead to yield increments of over 20% to a certain extent. MicroRNAs (miRNAs) were known to participate in the development and vigor of seed in plants, but its impact on seed vigor in two-line hybrid wheat remains poorly elucidated. Results The hybrid (BS1453/11GF5135) wheat exhibited superiority in seed vigor and anti-aging capacity, compared to its male parent (11GF5135, MP) and female parent (BS1453, FP). We identified four miRNAs associated with seed vigor, all of which are novel miRNAs. The majority of targets of miRNAs were related to ubiquitin ligases, kinases, sucrose synthases and hydrolases, involving in starch and sucrose metabolism, hydrolysis, catalysis, plant hormone signal transduction, and other pathways, which played crucial roles in seed development. Additionally, we also found miR531 was differentially expressed in both male parent and hybrid, and its target gene was a component of the E1 subunit of α-ketoate dehydrogenase complex, which interacted with dihydrolipoamide acetyltransferase (E2) and dihydrolipoyl dehydrogenase (E3). Finally, We established a presumptive interaction model to speculate the relationship of miR531 and seed vigor. Conclusions This study analyzed the seed vigor of two-line hybrid wheat, and screened seed vigor-related miRNAs. Meanwhile speculated the genetic relationship of hybrid and parents, in terms of miRNAs. Consequently, the present study provides new insights into the miRNA-mediated gene and protein interaction network that regulates seed vigor. These findings hold significance for enhancing the yield and quality of two-line hybrid wheat, facilitating its future applications.

Abstract Background The influence of the small Rho GTPase Rif (RHOF) on tumor growth, glycolysis, endothelial–mesenchymal transition (EMT), and the potential mechanism of RHOF in pancreatic cancer (PC) were explored. Methods RHOF expression in PC tissues and cells was assessed by qRT-PCR and western blotting. The viability, proliferation, apoptosis, migration, and invasion of PC cells were assessed using CCK-8, colony formation, EdU, flow cytometry, scratch, and Transwell assays. The expression of EMT- and glycolysis-related proteins was determined using western blotting. The potential mechanisms of action of RHOF in PC were identified using bioinformatic analysis. The effects of RHOF were assessed in vivo using a xenograft mouse model. Results PC cell proliferation, migration, and invasion are accelerated by RHOF overexpression, which inhibited apoptosis. RHOF overexpression promoted EMT and glycolysis as evidenced by a decrease in E-cadherin expression and an increase in N-cadherin, Vimentin, HK2, PKM2, and LDHA expression. Bioinformatic analysis indicated that RHOF activated EMT, glycolysis, and Myc targets and that c-Myc could bind to the PKM2 promoter. RHOF overexpression promotes the lactylation and nuclear translocation of Snail1. Silencing Snail1 reversed the promoting effects of RHOF and lactate on cell migration, invasion, and EMT. Moreover, in vivo tumor growth and EMT were inhibited by RHOF silencing. Conclusion RHOF plays an oncogenic role in PC. c-Myc is upregulated by RHOF and promotes PKM2 transcription. PKM2 further induces glycolysis, and the lactate produced by glycolysis causes the lactylation of Snail1, ultimately promoting EMT.

In this study, blackberry juice was fermented with Lactobacillus plantarum P-S1016. The growth kinetic parameters of this strain were determined, and the organic acids and flavor substances of fermented blackberry juice were analyzed. Besides, its flavor quality was tested using an electronic tongue (E-tongue). The protective effect of fermented blackberry juice against corticosterone-induced injury in PC12 cells was investigated by measuring cell viability, reactive oxygen species (ROS) level, apoptosis rate, and mitochondrial membrane potential. The results showed that the growth kinetic model of L. plantarum P-S1016 had excellent goodness of fit with a determination coefficient (R2) of 0.943, and the bacterial concentration reached a maximum value of 9.40 (lg (CFU/mL)) at 29.28 h. The contents of lactic acid and succinic acid in fermented blackberry juice were 38.99 and 3.30 mg/mL, respectively, and the contents of esters, alcohols, acids, and other flavor components increased compared with those in fresh blackberry juice, with alcohols accounting for the highest proportion (33.28%) of the total, followed by alkanes (29.80%); the saltiness of blackberry juice was significantly reduced after fermentation. In addition, fermented blackberry juice at concentrations of 50 and 200 µg/mL significantly increased the survival rate of cells induced by corticosterone by (1.48 ± 0.07) and (1.60 ± 0.01) folds, reduced intracellular ROS levels, late apoptosis rate and the proportion of necrotic cells, and inhibited the decrease of mitochondrial membrane potential. In conclusion, blackberry juice fermented with L. plantarum P-S1016 has good taste and flavor quality and strong neuroprotective potential. It is expected to become a new functional natural plant-based beverage, which is important for improving the edible properties and functional value of blackberry fresh fruits.

Abstract Oats (Avena sativa L.) are rich in nutrients and bioactive compounds, serving as a roughage source for ruminants. This study investigated the impact of lactic acid bacteria (LAB), cellulase (M), and their combinations (LM) on the fermentation quality and metabolic compounds of oat silage. Results demonstrated that all additive treatments significantly increased lactic acid content compared to the control group (P

Abstract Background The study aimed to identify the optimal model for predicting rectal cancer liver metastasis (RCLM). This involved constructing various prediction models to aid clinicians in early diagnosis and precise decision-making. Methods A retrospective analysis was conducted on 193 patients diagnosed with rectal adenocarcinoma were randomly divided into training set (n = 136) and validation set (n = 57) at a ratio of 7:3. The predictive performance of three models was internally validated by 10-fold cross-validation in the training set. Delineation of the tumor region of interest (ROI) was performed, followed by the extraction of radiomics features from the ROI. The least absolute shrinkage and selection operator (LASSO) regression algorithm and multivariate Cox analysis were employed to reduce the dimensionality of radiomics features and identify significant features. Logistic regression was employed to construct three prediction models: clinical, radiomics, and combined models (radiomics + clinical). The predictive performance of each model was assessed and compared. Results KRAS mutation emerged as an independent predictor of liver metastasis, yielding an odds ratio (OR) of 8.296 (95%CI: 3.471–19.830; p

The hot deformation behavior of 30MnB5V steel was experimentally investigated and theoretically analyzed using phenomenological constitutive models and an ensemble learning algorithm. Hot compression experiments were conducted with an MMS-200 thermo-mechanical simulation machine on the 30MnB5V steel at strain rates of 0.01–10 s−1 and temperatures of 950–1150 °C. The characteristics of the true stress-strain curves under different conditions and the corresponding microstructural evolutions were examined in detail. The results indicate that raising the temperature or lowering the strain rate promotes dynamic recrystallization. As temperature decreases or strain rate increases, the degree of recrystallization softening declines, and stress-strain curves transition from recrystallization to sustained work hardening or dynamic recovery types. Subsequently, the strain-compensated Arrhenius model, modified Johnson-Cook (J-C) model, and Bayesian-optimized LightGBM (BO-LightGBM) model were constructed sequentially to predict the flow stress of the tested steel. The accuracy of the three models was evaluated using the coefficient of determination (R2), mean absolute error (MAE), root mean square error (RMSE), and mean absolute percentage error (MAPE). The results reveal that the accuracy of the BO-LightGBM model is significantly higher than that of the Arrhenius model and the modified J-C model. Finally, three-dimensional power dissipation maps and hot processing maps were established under various strain conditions. The results suggest that the tested steel demonstrates good workability at deformation temperatures of 1075–1125 °C and strain rates of 0.03–0.22 s−1.

Objective To identify the characteristics of nutritional problems in patients with Parkinsonism who participated in multi-disciplinary team (MDT) and to investigate the correlation between nutritional status and dysphagia in these patients. The predictive value of video fluoroscopic swallowing study (VFSS) and EAT-10 scale for malnutrition was compared. Methods Subjects were patients with Parkinsonism participated in joint MDT consultation project in Peking Union Medical College Hospital from November 2020 to January 2023. Subjective and objective dysphagia were evaluated by EAT-10 scale score and VFSS dysphagia score. Nutritional status of the patients was evaluated by geriatric nutrition risk index (GNRI), albumin, prealbumin, serum folic acid, vitamin B12 and temporal muscle thickness. Results A total of 30 participants met the criteria and were included in the study. The age was 45-82 (66.1±9.0) years old. Six (20%) were at risk of malnutrition shown b a comprehensive nutritional status assessment using GNRI. The areas under receiver operating characteristic(ROC) curves(AUC) of VFSS dysphagia score and EAT-10 score to predict malnutrition were 0.781 (0.568-0.995) and 0.927 (0.827-1.000), respectively. EAT-10 score was correlated with GNRI(r=-0.524, P＜0.01), BMI(r=-0.618, P＜0.001), prealbumin (r=-0.616, P＜0.001). The VFSS dysphagia score was only correlated with BMI (r=-0.446, P＜0.05) and prealbumin(r=-0.387, P＜0.05). Conclusions Patients with Parkinsonism requiring MDT often have multiple micronutrient imbalance. Patients′ subjective perception of dysphagia has a greater impact on their nutritional status than objective assessment of dysphagia.

Abstract Currently, surgical resection remains the primary approach for treating oral squamous cell carcinoma (OSCC), with limited options for effective drug therapy. Cardamonin, a principal compound derived from Myristica fragrans of the Zingiberaceae family, has garnered attention for its potential to suppress the onset and progression of various malignancies encompassing breast cancer, hepatocellular carcinoma, and ovarian cancers. Nevertheless, the involvement of cardamonin in the treatment of OSCC and its underlying mechanisms are yet to be elucidated. This research explored the possible target of cardamonin in treating OSCC via network pharmacological analysis. Subsequently, this research investigated the impact of cardamonin on OSCC cells via in vitro experiments, revealing its capacity to impede the migration, proliferation, and invasion of OSCC cells. Additionally, western blotting analysis demonstrated that cardamonin facilitates apoptosis by regulating the PI3K/AKT pathway. The findings suggest that MMP9 and the PI3K/AKT signaling pathway may serve as the target and pathway of cardamonin in treating OSCC. To summarize, the research findings suggest that cardamonin may facilitate apoptosis in OSCC cells by inhibition of PI3K/AKT pathway activation. These outcomes offer a theoretical basis for the utilization of cardamonin as a natural drug for treating OSCC.

Abstract Background Nasopharyngeal carcinoma (NPC) is diagnosed relatively late and has a poor prognosis, requiring early detection to reduce the disease burden. This diagnostic test accuracy meta-analysis evaluated the serological diagnostic value of nine EBV-related IgA antibody panels (EBNA1-IgA, VCA-IgA, EA-IgA, Zta-IgA, EBNA1-IgA + VCA-IgA, VCA-IgA + EA-IgA, VCA-IgA + Rta-IgG, EBNA1-IgA + VCA-IgA + Zta-IgA and VCA-IgA + EA-IgA + Rta-IgG), aiming to identify suitable serological detection biomarkers for NPC screening. Methods PubMed, Embase, China National Knowledge Infrastructure and Chinese BioMedical Literature Database were searched from January 1st, 2000 to September 30th, 2023, with keywords nasopharyngeal carcinoma, IgA, screening, early detection, early diagnosis, sensitivity and specificity. Articles on the diagnostic value of serum EBV-related IgA antibody panels for NPC were included. Study selection, data extraction, and quality assessment were performed independently by two researchers, and a third researcher was consulted in the case of disagreement. Bivariate models were used for statistical analysis. The quality of included studies was evaluated through Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). Results A total of 70 articles were included, involving 11 863 NPC cases and 34 995 controls. Among the nine EBV-related IgA antibody panels, EBNA1-IgA + VCA-IgA [0.928 (0.898, 0.950)], VCA-IgA + Rta-IgG [0.925 (0.890, 0.949)], EBNA1-IgA + VCA-IgA + Zta-IgA [0.962 (0.909, 0.985)] and VCA-IgA + EA-IgA + Rta-IgG [0.945 (0.918, 0.964)] demonstrated higher pooled sensitivity (95%CI). In terms of diagnostic odds ratio (DOR) (95%CI), EBNA1-IgA + VCA-IgA [107.647 (61.173, 189.430)], VCA-IgA + Rta-IgG [105.988 (60.118, 186.857)] and EBNA1-IgA + VCA-IgA + Zta-IgA [344.450 (136.351, 870.153)] showed superior performance. Additionally, the SROC curves for EBNA1-IgA + VCA-IgA and VCA-IgA + Rta-IgG were more favorable. However, publication bias was detected for VCA-IgA (P = 0.005) and EBNA1-IgA + VCA-IgA (P = 0.042). Conclusions In general, parallel detection of serum EBNA1-IgA, VCA-IgA and Zta-IgA antibodies using ELISA demonstrates better pooled sensitivity and DOR among the studied panels. In the cases where fewer indicators are used, serum VCA-IgA and EBNA1-IgA/Rta-IgG antibody panel exhibits a comparable performance. Trial registration The International Prospective Register of Systematic Reviews registration number: CRD42023426984, registered on May 28, 2023.

Olfaction, the sense of smell, is crucial for animal survival, especially in localizing prey or food. However, little is known about the fish behavioral responses to specific food odors and which olfactory receptor might be activated by the food odors. Here, we examined the evolutionary relationships and classified the subfamilies of olfactory receptors (ORs), and conducted behavioral and gene expression analysis in grass carp (Ctenopharyngodon idellus). We identified 196 intact ORs in the grass carp genome and classified them into 8 subfamilies: β, δ, ε, η, γ, κ, θ, and ζ. 12 representative ORs (4 β, 4 δ, and 4 ε) were highly expressed in the olfactory epithelium (OE) of 24-month-old grass carp. Behavioral exploration found that grass carp showed different behaviors to different food odors at a series of concentrations. Specifically, 0.01 μmol/L amino acid mixtures and 0.005 × Hydrilla verticillata extracts strongly changed the preference index and swimming trajectories in 6-month-old grass carp. In addition, the two food odors stimulation differentially induced ORs expression in three tissues, especially strong in the olfactory bulb and brain. Altogether, our results suggest that olfaction plays an important role in the regulation of fish feeding behavior and provide a basis for further studies on the function and specific recognition of olfactory receptors in fish.

Nano zero-valent iron (nZVI) and sulfidation-modified nZVI (S-nZVI) were synthesized and used to remove hexavalent chromium (Cr(VI)) in wastewater. Characterization of the products showed that the sulfidation process significantly changed the morphology of nZVI, with enhanced crystallinity. The effects of S/Fe ratio, pH value, and reaction temperature on Cr(VI) removal were studied. A S/Fe ratio of 0.5 was the most appropriate parameter, with a removal efficiency of 98% in the condition of pH = 2. The effects of anions (Cl−, NO3−, CO32−, and SO42−) and cations (Ca2+ and Mg2+) on the Cr(VI) removal efficiency were investigated, and the relevant mechanisms were discussed. The Cr(VI) removal efficiency of S-nZVI was significantly greater than that of nZVI, mainly owing to the existence of FeS layers that could protect Fe0 cores and prompt electron transfer. The aging and cycling experiments showed that S-nZVI could maintain its reactivity when facing the corrosion of water, and showed cycling stability. Thus, S-nZVI is an effective and feasible agent for the remediation of Cr(VI)-contained wastewater.

Vascular calcification and vascular ageing are “silent” diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N6-methyladenosine (m6A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m6A methylation.

Abstract This study introduces a novel self-supervised learning method for single-frame subtraction and vessel segmentation in coronary angiography, addressing the scarcity of annotated medical samples in AI applications. We pretrain a U-Net model on a large dataset of unannotated coronary angiograms using an image-to-image translation framework, then fine-tune it on a limited set of manually annotated samples. The pretrained model excels at comprehensive single-frame subtraction, outperforming existing DSA methods. Fine-tuning with just 40 samples yields a Dice coefficient of 0.828 for vessel segmentation. On the public XCAD dataset, our model sets a new state-of-the-art benchmark with a Dice coefficient of 0.755, surpassing both unsupervised and supervised learning approaches. This method achieves robust single-frame subtraction and demonstrates that combining pretraining with minimal fine-tuning enables accurate coronary vessel segmentation with limited manual annotations. We successfully apply this approach to assist physicians in visualizing potential vascular stenosis sites during coronary angiography. Code, dataset, and a live demo will be available available at: https://github.com/newfyu/DeepSA .

Abstract Renal cell carcinoma (RCC) is one of the most common tumors that afflicts the urinary system, accounting for 90–95% of kidney cancer cases. Although its incidence has increased over the past decades, its pathogenesis is still unclear. Tumor-associated macrophages (TAMs) are the most prominent immune cells in the tumor microenvironment (TME), comprising more than 50% of the tumor volume. By interacting with cancer cells, TAMs can be polarized into two distinct phenotypes, M1-type and M2-type TAMs. In the TME, M2-type TAMs, which are known to promote tumorigenesis, are more abundant than M1-type TAMs, which are known to suppress tumor growth. This ratio of M1 to M2 TAMs can create an immunosuppressive environment that contributes to tumor cell progression and survival. This review focused on the role of TAMs in RCC, including their polarization, impacts on tumor proliferation, angiogenesis, invasion, migration, drug resistance, and immunosuppression. In addition, we discussed the potential of targeting TAMs for clinical therapy in RCC. A deeper understanding of the molecular biology of TAMs is essential for exploring innovative therapeutic strategies for the treatment of RCC.

Abstract The primary aim of this investigation was to leverage radiomics features derived from contrast-enhanced abdominal computed tomography (CT) scans to devise a predictive model to discern the benign and malignant nature of intraductal papillary mucinous neoplasms (IPMNs). Radiomic signatures were meticulously crafted to delineate benign from malignant IPMNs by extracting pertinent features from contrast-enhanced CT images within a designated training cohort (n = 84). Subsequent validation was conducted with data from an independent test cohort (n = 37). The discriminative ability of the model was quantitatively evaluated through receiver operating characteristic (ROC) curve analysis, with the integration of carefully selected clinical features to improve the comparative analysis. Arterial-phase images were utilized to construct a model comprising 8 features for distinguishing between benign and malignant cases. The model achieved an accuracy of 0.891 [95% confidence interval (95% CI), 0.816–0.996] in the cross-validation set and 0.553 (95% CI 0.360–0.745) in the test set. Conversely, employing 9 features from the venous-phase resulted in a model with a cross-validation accuracy of 0.862 (95%CI 0.777–0.946) and a test set accuracy of 0.801 (95% CI 0.653–0.950).Integrating the identified clinical features with imaging features yielded a model with a cross-validation accuracy of 0.934 (95% CI 0.879–0.990) and a test set accuracy of 0.904 (95% CI 0.808–0.999), thereby further improving its discriminatory ability. Our findings distinctly illustrate that venous-phase radiomics features eclipse arterial-phase radiomic features in terms of predictive accuracy regarding the nature of IPMNs. Furthermore, the synthesis and meticulous screening of clinical features with radiomic data significantly increased the diagnostic efficacy of our model, underscoring the pivotal importance of a comprehensive and integrated approach for accurate risk stratification in IPMN management.

Objective To summarize the experience of nursing care of patients with severe alopecia areata treated with topical diphenylcyclopropenone. Methods Seventeen patients with severe alopecia areata treated with topical diphenylcyclopropenone were enrolled. Before the treatment, self-protection was given to the therapist and informed consent was given to the patients. During the treatment, the principles of procedure and drug dosages were strictly followed. After the treatment, WeChat APP was used in the follow-up management of patients. This management included one-to-one evaluation of and consultation on efficacy, adverse reactions, diet and psychology. Results Seventeen patients completed the 16-week treatments, with an effective rate of 58.82%. The adverse reactions were mild and controllable. The therapists did not experience any adverse reactions such as allergic reactions. Conclusion In the treatment of severe alopecia areata with topical diphenylcyclopropenone, appropriate pre-operative preparation and post-operative care can effectively improve the patient's compliance and the therapeutic efficacy.

Abstract Fermenting Chinese medicinal herbs could enhance their bioactivities. We hypothesized probiotic-fermented gastrodia elata Blume (GE) with better potential to alleviate insomnia than that of unfermented, thus the changes in chemical composition and the insomnia-alleviating effects and mechanisms of fermented GE on pentylenetetrazole (PTZ)-induced insomnia zebrafish were explored via high-performance liquid chromatography (HPLC) and mass spectroscopy-coupled HPLC (HPLC-MS), phenotypic, transcriptomic, and metabolomics analysis. The results demonstrated that probiotic fermented GE performed better than unfermented GE in increasing the content of chemical composition, reducing the displacement, average speed, and number of apoptotic cells in zebrafish with insomnia. Metabolomic investigation showed that the anti-insomnia effect was related to regulating the pathways of actin cytoskeleton and neuroactive ligand-receptor interactions. Transcriptomic and reverse transcription qPCR (RT-qPCR) analysis revealed that secondary fermentation liquid (SFL) significantly modulated the expression levels of neurod1, msh2, msh3, recql4, ercc5, rad5lc, and rev3l, which are mainly involved in neuron differentiation and DNA repair. Collectively, as a functional food, fermented GE possessed potential for insomnia alleviation.

T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens, thereby engaging with CD3 on the T cell receptor. This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells. These antibodies have emerged as one of the most promising avenues within tumor immunotherapy. However, despite success in treating hematological malignancies, significant advancements in solid tumors have yet to be explored. In this review, we aim to address the critical challenges associated with T cell-redirecting bispecific antibodies and explore novel strategies to overcome these obstacles, with the ultimate goal of expanding the application of this therapy to include solid tumors.

The development of the nigrostriatal dopaminergic (DA) pathway in the brain involves many transcriptional and chemotactic molecules, and a deficiency of these molecules can cause nigrostriatal tract defects. However, the role of the end product, dopamine, in nigrostriatal pathway development has not been described. In the present study, we analyzed a mouse model of congenital dopamine and serotonin deficiency, namely, the aromatic l-amino acid decarboxylase (AADC) deficiency (DdcKI) mouse model. We found via tyrosine hydroxylase (TH) immunofluorescence staining that the number of DA fibers in the stratum of 14-day-old DdcKI mice decreased. In TH-stained cleared whole brains of DdcKI mice, the numbers of DA neurons in the substantia nigra (SN) and the number of DA nerve bundles leaving the SN were both normal. However, we found that the nigrostriatal bundles in DdcKI mice were dispersed, taking aberrant routes to the striatum and spreading over a wide area. The total volume occupied by the nigrostriatal tract was increased, and the fraction of TH staining in the tract was decreased in DdcKI mice. Single-nucleus RNA sequencing analysis for mice 0, 7, and 14 days of age, revealed delayed axonogenesis and synapse formation in the striatum of DdcKI mice. The CellChat program inferred less cell–cell communication between striatal D1/D2 neurons but increased cell–cell communication involving neural precursors in DdcKI mice. Therefore, a congenital deficiency in dopamine affects nigrostriatal axon extension and striatal innervation. These nigrostriatal tract defects may limit the treatment efficacy for patients with TH or AADC deficiency.

Background: Acupressure has proven efficacy in symptoms management, making it valuable in clinical practice and patient care. Given the rising number of increasing publications on acupressure, we aimed to analyze the literature from the past 20 years and provided current trends and hotspot for future research directions. Methods: Publications on acupressure from January 1, 2004 through May 1, 2024 were retrieved from the Web of Science database. The extracted records underwent thorough analysis based on publication year, research area, journal, countries/regions, organization, authors, and keywords. The bibliometric analysis was conducted using Citespace and Microsoft Excel software. Results: Of the 1,929 screened records, 770 publications were identified. The annual number of acupressure has gradually increased, with the 45 % of the total publication occurring from 2020 to 2024. Among countries and institutions, China (252 articles) and Hong Kong Polytechnic University (41 articles) have the highest number of publications. Notably, USA and Hong Kong Polytechnic University exhibits the highest centrality score in cooperative network among countries/regions and institutions. Chao Hsing Yeh from the Cizik School of Nursing, University of Texas Health Science Center, was the most prolific author with 22 papers. Evidence-Based Comple Alt, with 53 articles, is the journal with the most publications. According to the keyword, timeline diagram and prominence mapping analysis, we believe that “insomnia”, “labor”, “waist circumference”, “reliability” and “vagus nerve stimulation” related clusters may be new hotspots in the field of acupressure. Conclusion: This study presents the research trajectory of acupressure over the past 20 years, providing a foundation for future research and highlighting the significant contributions of nursing researchers. By analyzing research trends and hotsport, nursing professionals can integrate acupressure more effectively into holistic patient care, improving quality of life, and contributing to traditional Chinese medicine.

IntroductionImmunogenic cell death (ICD) is capable of activating the anti-tumor immune response of the organism; however, it is concurrently a complex process involving multiple factors. The specific factors that impact the occurrence of ICD remain undefined.MethodsThrough cluster analysis, patient specimens retrieved from the TARGET, TCGA, and GEO AML databases were categorized into two subtypes based on the expression levels of ICD-related genes: ICD-high and ICD-low. We compared the prognostic survival outcomes, pathway enrichment analysis, and immune cell infiltration between these two subtypes. Additionally, we identified factors related to AML development from multiple databases and verified the role of these factors both in vivo and in vitro in activating the immune response during the occurrence of ICD. Results and discussionIn the ICD-high subtype, there was a notable increase in the abundance of immune cell populations, along with the enrichment of pathways pertinent to the activation of various immune cells. Despite these immunological enhancements, this subgroup demonstrated a poorer prognosis. This phenomenon was consistently observed across various additional AML datasets, leading us to hypothesize that elevated expression of ICD genes does not invariably correlate with a favorable prognosis. Notably, STK10 exhibited elevated expression in AML, was associated with a poor prognosis, and showed synchronous expression patterns with ICD genes. Inhibition of STK10 led to the activation of ICD and the induction of an antitumor response. Moreover, when combined with other ICD inducers, it produced a synergistic anti-tumor effect. Our results reveal the impact of STK10 on ICD and underscore its key role in initiating ICD.

Abstract The passive sensing and active control of electromagnetic (EM) waves have always been attractive in electronic and information areas, especially during the intelligent era. Here a new method is presented to achieve the angle sensing of incident wave and adaptive control of backward scattering using the intelligent metasurface. The proposed unit cells have the ability to dynamically manipulate the receiving and reflection of the EM energy respectively. The angle sensing of incident waves can be actualized using the method of compressive sensing based on multiple receiving patterns, which are generated by randomly switching the receiving and reflection states of the unit cells. Afterward, the customized performances of backward scattering waves according to the cognitive incident angle can be realized by controlling the programmable reflective phases of unit cells correspondingly. One prototype composed of the metasurface and the module for sensing and adaptive feedback control is fabricated. The whole intelligent metasurface with customizing the function of retro‐reflection or low scattering is measured without human intervention and the good results acquired can verify the validity of the proposed concept and design.

Gene expression is regulated by transcription factors binding to cis-elements in promoters. However, efficient cis-elements for genetic engineering are rarely reported. In this study, we identified an 11 bp cis-element in the PtoCP1 promoter that drives strong constitutive gene expression in Populus tomentosa. A 2,270 bp promoter region upstream of the PtoCP1 gene’s translation start site was cloned and named ProPtoCP1. This promoter controls GUS reporter gene expression in the roots, leaves, and stems of Arabidopsis seedlings. Based on the location and density of cis-elements, the PtoCP1 promoter was divided into four fragments by 5′-end deletions. GUS staining and RT-qPCR revealed a key cis-element at −466 to −441 bp essential for gene expression. Further analysis showed that the MYB-TGACG cis-element is a positive regulator, whereas neither MYB nor TGACG alone drove gene expression. This study enhances our understanding of gene expression regulation by cis-elements and provides a valuable tool for genetic engineering.

BackgroundMore and more patients with pancreatic cancer (PC) received neoadjuvant therapy (NAT) and then underwent radical pancreatectomy. However, the benefit of adjuvant chemotherapy (AC) for these patients is still controversial. This study is designed to determine the benefits of postoperative AC for patients with PC undergoing NAT and radical resection.MethodsWe conducted a comprehensive search of the PubMed, Embase, Web of Science, and Cochrane Library databases, covering the period from their inception until 10 September 2023. Our analysis focused on the assessment of overall survival (OS) and recurrence-free survival (RFS) through meta-analysis. The fixed-effects model and the random-effects model were used to process the data. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were employed to determine the necessary of administering AC for patients with PC who have undergone NAT and radical resection. We retrieved 3,063 search results, of which 3,048 were excluded because of duplication or after applying our inclusion and exclusion criteria.ResultsA total of 15 studies with 21,113 patients (7,794 patients in the AC group and 13,319 in the non-AC group) were included, all of which reported OS, and three studies reported disease-free survival (DFS)/tumor-specific survival (CSS)/RFS. The final results showed that AC significantly improved OS and DFS/CSS/RFS in patients with PC who underwent pancreatectomy after NAT [OS: HR = 0.80, 95% CI (0.75∼0.86), P < 0.00001, I2 = 48%; DFS/CSS/RFS: HR = 0.53, 95% CI (0.41~0.69), P < 0.00001, I2 = 0%]. Furthermore, we performed subgroup analyses and demonstrated that AC provided a significant survival benefit for patients with PC after NAT and resection regardless of the tumor size [

ABSTRACT Objective This study explored the distributions of gastric mucosal status and their links to gastric cancer within urban high‐risk individuals in China. Methods From 2014 to 2015, a questionnaire survey was administered among individuals aged 40 to 69 years, residing for over 3 years in seven selected cities across China. Utilizing the questionnaire data, high‐risk individuals for gastric cancer were screened. These identified high‐risk individuals were invited to undergo endoscopy, followed by pathological examinations conducted for those with suspicious lesions. Prior cancer patients and those newly diagnosed with gastric cancer were excluded, and the remaining endoscopic participants were prospectively followed up until December 2021. Results The prospective study followed 8911 individuals at high risk of gastric cancer for a median duration of 6.77 years. The incidence density of gastric cancer was 58.55 per 100,000 person‐years. At baseline, the distributions of subjects across normal gastric mucosa, gastritis/ulcer/polyp, atrophic gastritis/intestinal metaplasia, and intraepithelial neoplasia groups were 47.09%, 36.27%, 9.57%, and 7.07%, respectively. Compared with normal gastric mucosa, the hazard ratios (HRs) for gastric cancer in the other groups were 0.89 [95% confidence interval (95%CI): 0.38–2.08], 1.52 (95%CI: 0.50–4.66), and 4.63 (95%CI: 1.98–10.82). When using the 40–54 age group as the reference, the HR for 55–69 age group was 3.49 (95%CI: 1.52–7.98). Conclusion Among high‐risk individuals with gastric cancer, the proportions of individuals exhibiting different gastric mucosal status inversely correlated with the severity of mucosal lesions, whereas the risk of gastric cancer progressively escalated with the increasing severity of mucosal lesions and advancing age.

Osteosarcoma stands as the most prevalent bone tumor, characterized by a heightened tendency for local recurrence and distant metastasis, resulting in a bleak prognosis. Presently, there exists a shortage of novel markers to effectively determine the prognosis of osteosarcoma patients. Recent research indicates that hematological markers partially mirror an individual’s microenvironment, offering potential insights into predicting patient prognosis. However, prior studies predominantly focused on the prognostic significance of singular hematological indices, failing to comprehensively represent the tumor microenvironment of patients. In our investigation, we meticulously gathered data on 22 hematological and electrolyte markers, utilizing LASSO Cox regression analysis to devise an Electrolyte Prognostic Scoring System (EPSS). The EPSS encompasses various indicators, including immunity, inflammation, coagulation, and electrolyte levels. Our findings indicate that the EPSS stands as an independent prognostic factor for overall survival among osteosarcoma patients. It serves as a valuable addition to clinical characteristics, adept at discerning high-risk patients from those deemed clinically low-risk. Furthermore, EPSS-based nomograms demonstrate commendable predictive capabilities.

Background: Progressive supranuclear palsy (PSP) is characterized by the presence of hyperphosphorylated and misfolded tau aggregates in neurons and glia. Recent studies have illuminated the prion-like cell-to-cell propagation of tau via exosomes. Recognizing the potential significance of excretion through urine as a crucial pathway for eliminating pathological tau from the central nervous system, this study aimed to investigate whether exosomes derived from the urine of PSP-Richardson's syndrome (PSP-RS) patients can elicit tau pathology and PSP-like symptoms in mice. Methods: Urinary exosomes obtained from PSP-RS patients and normal controls (NCs) were stereotactically injected into the bilateral globus pallidus of mouse brains. Behavioral analyses were conducted every 3 months post-injection. After 6 months, mice were sacrificed for pathological evaluation. Results: Elevated levels of phosphorylated tau and neural cell markers were observed in urinary exosomes from PSP-RS patients compared to NCs. At the 6-month mark post-injection, tau inclusions were evident in the brains of mice receiving urinary exosomes from PSP-RS patients, with widespread distribution in both injection sites and distant brain regions (cortex, hippocampus, and substantia nigra). Tau pathology manifested in neurons and astrocytes. Moreover, mice injected with urinary exosomes from PSP-RS patients exhibited impaired motor coordination and balance, mirroring PSP motor symptoms. Conclusion: Our findings indicate that urinary exosomes from PSP-RS patients can induce tau pathology and trigger PSP-like motor symptoms in mice. This leads to the hypothesis that exosomes may play a role in the pathogenesis of PSP.

IntroductionWe described how COVID-19 fatality and symptoms varied by dominant variant and vaccination in the US.MethodsUsing the Restricted Access Dataset from the US CDC (1/1/2020–10/20/2022), we conducted a cross-sectional study assessing differences in COVID-19 deaths, severity indicators (hospitalization, ICU, pneumonia, abnormal X-ray, acute respiratory distress syndrome, mechanical ventilation) and 12 mild symptoms by dominant variant/vaccination periods using logistic regression after controlling for confounders.ResultsWe found the highest fatality during the dominant periods of Wild (4.6%) and Delta (3.4%). Most severe symptoms appeared when Delta was dominant (Rate range: 2.0–9.4%). Omicron was associated with higher mild symptoms than other variants. Vaccination showed consistent protection against death and severe symptoms for most variants (Risk Ratio range: 0.41–0.93). Boosters, especially the second, provided additional protection, reducing severe symptoms by over 50%.DiscussionThis dataset may serve as a useful tool to monitor temporospatial changes of fatality and symptom for case management and surveillance.

Although advancements in genomic and epigenetic research have deepened our understanding of acute myeloid leukemia (AML), only one-third of patients can achieve durable remission. Growing evidence suggests that the immune microenvironment in bone marrow influences prognosis and survival in AML. There is a specific association between CD8+ T cells and the prognosis of AML patients. To develop a CD8+ T cell-related immune risk score for AML, we first evaluated the accuracy of CIBERSORTx in predicting the abundance of CD8+ T cells in bulk RNA-seq and found it significantly correlated with observed single-cell RNA sequencing data and the proportions of CD8+ T cells derived from flow cytometry. Next, we constructed the CTCG15, a 15-gene prognostic signature, using univariate and LASSO regression on the differentially expressed genes between CD8+ THigh and CD8+ TLow groups. The CTCG15 was further validated across six datasets in different platforms. The CTCG15 has been shown to be independent of established prognostic markers, and can distill transcriptomic consequences of several genetic abnormalities closely related to prognosis in AML patients. Finally, integrating this model into the 2022 European LeukemiaNet contributed to a higher predictive power for prognosis prediction. Collectively, our study demonstrates that CD8+ T cell-related signature could improve the comprehensive risk stratification and prognosis prediction in AML.

The effective containment of fission products (FPs) within tri-structural isotropic (TRISO) fuel particles is crucial for the safety and efficiency of High Temperature Gas-cooled Reactors (HTGRs). Combining multi-scale (µm to nm) and multi-dimensional (2D and 3D) analysis, this study focuses on the migration mechanisms of silver (Ag), for which the Ag-110 m FP isotope is radiotoxic, facilitated by reactions with palladium (Pd) alloys and the silicon carbide (SiC) layer at elevated temperatures (1300–1500 °C). Three primary pathways for Ag migration are identified: (1) diffusion in solid palladium silicide to form (Pd,Ag)2Si, (2) infiltration through cracks and pores in the carbon phase, and (3) liquid phase migration along SiC grain boundaries. Especially at temperatures above the melting point of Pd2Si (1404 °C), a ‘dissolution-recrystallisation’ mechanism is proposed of the Ag-Pd-Si liquid phase migrating along SiC grain boundaries. The study employs state-of-the-art in-situ heating transmission electron microscopy (TEM) techniques to directly observe the dynamic migration processes of Pd silicide within SiC, providing unprecedented insights into the liquid behaviour in TRISO fuel. These findings highlight the significant role of liquid phases in determining the transport of FPs through the TRISO-SiC which is vital for developing strategies that enhance the safety and efficacy of HTGRs.

Abstract Background Emerging evidence indicates carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the development of atherosclerosis (AS). However, the roles and functions of CEACAM1 in AS remain unknown. Therefore, this study aims to investigate the roles and molecular functions of CEACAM1 in AS. Methods We constructed a diabetes mellitus (DM) + high-fat diet (HFD) mouse model based on the streptozotocin (STZ)-induced apolipoprotein E-knockdown (ApopE−/−) mouse to investigate the roles and regulatory mechanism of miR-449a/CEACAM1 axis. The mRNA expression and protein levels in this study were examined using quantity PCR, western blot, immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC), respectively. And the lipid deposition and collagen content were detected using Oil Red O and Sirius Red staining. Cell apoptosis, migration, invasion, and tuber formation were detected by Annexin-V FITC/PI, wound healing, transwell, and tuber formation assays, respectively. The relationship between miR-449a and CEACAM1 was determined by a dual-luciferase reporter gene assay. Results miR-449a and MMP-9 were upregulated, and CEACAM1 was downregulated in the DM + HFD MOUSE model. Upregulation of CEACAM1 promoted atherosclerotic plaque stability and inhibited inflammation in the DM + HFD mouse model. And miR-449a directly targeted CEACAM1. Besides, miR-449a interacted with CEACAM1 to regulate atherosclerotic plaque stability and inflammation in DM-associated AS mice. In vitro, the rescue experiments showed miR-449a interacted with CEACAM1 to affect apoptosis, migration, invasion, and tuber formation ability in high glucose (HG)-induced HUVECs. Conclusion These results demonstrated that miR-449a promoted plaque instability and inflammation in DM and HFD-induced mice by targeting CEACAM1.

An unmanned surface vessel(USV) single-platform is easily restricted by the platform during surface mission execution, and the construction of a cross-platform system for USVs and unmanned aerial vehicles(UAVs) can realize the complementary advantages of the platform. In this paper, the take-off and landing and energy replenishment technologies of USVs and UAVs were studied to realize the enduring cooperative operation of USVs and UAVs. Firstly, for the problem of UAV taking off and landing on dynamic USVs, the research on cooperative positioning take-off and landing technologies for USVs and UAVs was carried out, and the dynamic update model of speed and position information of USVs and UAVs was studied, realizing high-precision take-off and landing of UAVs at the USV end. Secondly, to address the problem of the short endurance time of UAVs, the research on UAV replenishment at the USV end was carried out, and the take-off and landing mechanism at the UAV end and the charging mechanism at the USV end were investigated to realize the rapid replenishment of UAVs landing on the USV. Finally, the performance of the cross-platform take-off and landing and energy replenishment system for USVs and UAVs was verified at sea. In the test, UAVs could land at the USV end and get energy replenished at the high-speed movement of 3.0 m/s of the USV-UAV system, meeting the demand of cross-platform mission execution by USVs and UAVs at sea.

Abstract Chimeric antigen receptors (CAR) are engineered fusion proteins that target T-cells to specific surface antigens of tumor cells to generate effective anti-tumor responses. CAR T-cell therapy is playing an increasingly important role in the treatment of relapsed/refractory B-cell malignancies (R/R BCM). Attempting to make CAR T-cells safer and more effective in treating R/R BCM, various novel engineered CAR T-cell agents are currently in the research and development or clinical trial stages. We have summarized here the latest reports on the novel CAR T-cell therapies for R/R BCM presented at the 2023 ASH Annual Meeting as well as the latest updates in related clinical trials.

Abstract Background Rwanda has aimed to rebuild its health care system since the Rwandan genocide against the Tutsis in 1994, though one of the challenges has been a scarcity of radiologic resources. Objective To assess the location and accessibility of radiologic facilities in Rwanda using geospatial mapping and population-based data. Methods A cross-sectional study was conducted in May 2023 using location and radiologic modality data provided by the Department of Radiology at the University Teaching Hospital of Kigali and the WorldPop database, a publicly available database providing open-access geospatial population data. Radiologic equipment included magnetic resonance (MR), computed tomography (CT), positron emission tomography (PET), radiotherapy, X-ray, mammography, and fluoroscopy machines. Geospatial analysis was performed using ArcGIS Pro 2.8.6 software. Results Fifty-six radiologic facilities were identified, including 5 MR, 7 CT, 1 radiotherapy, 52 X-ray, 5 mammography, 5 fluoroscopy, and 0 PET machines. There were 0.4 MR, 0.5 CT, 0 PET, 0.1 radiotherapy, 3.9 X-ray, 0.4 mammography, and 0.4 fluoroscopy units per 1 million people. Conclusion Rwanda is one of the countries with the lowest radiologic access in East Africa; however, there is evidence of progress, particularly in more advanced diagnostic imaging techniques such as computed tomography and magnetic resonance imaging. Critical relevance statement This study provides a 10-year update on current radiologic resources and access in Rwanda, identifying areas of progress and ongoing scarcity, serving as a guide for future direction of growth. Key points • As Rwanda works on rebuilding its health care system, this study provides an assessment of the current radiologic resources within the country. • There is less than one radiologic unit for every million of the Rwandan population for every imaging modality other than X-ray. • While radiologic access in Rwanda lags behind that of its neighbors, there has been growth focused on advanced imaging modalities and the training of human resources. Graphical Abstract

Abstract The pathogenesis of Parkinson’s disease (PD) is strongly associated with neuroinflammation, and type I interferons (IFN-I) play a crucial role in regulating immune and inflammatory responses. However, the specific features of IFN in different cell types and the underlying mechanisms of PD have yet to be fully described. In this study, we analyzed the GSE157783 dataset, which includes 39,024 single-cell RNA sequencing results for five PD patients and six healthy controls from the Gene Expression Omnibus database. After cell type annotation, we intersected differentially expressed genes in each cell subcluster with genes collected in The Interferome database to generate an IFN-I-stimulated gene set (ISGs). Based on this gene set, we used the R package AUCell to score each cell, representing the IFN-I activity. Additionally, we performed monocle trajectory analysis, and single-cell regulatory network inference and clustering (SCENIC) to uncover the underlying mechanisms. In silico gene perturbation and subsequent experiments confirm NFATc2 regulation of type I interferon response and neuroinflammation. Our analysis revealed that microglia, endothelial cells, and pericytes exhibited the highest activity of IFN-I. Furthermore, single-cell trajectory detection demonstrated that microglia in the midbrain of PD patients were in a pro-inflammatory activation state, which was validated in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model as well. We identified transcription factors NFATc2, which was significantly up-regulated and involved in the expression of ISGs and activation of microglia in PD. In the 1-Methyl-4-phenylpyridinium (MPP+)-induced BV2 cell model, the suppression of NFATc2 resulted in a reduction in IFN-β levels, impeding the phosphorylation of STAT1, and attenuating the activation of the NF-κB pathway. Furthermore, the downregulation of NFATc2 mitigated the detrimental effects on SH-SY5Y cells co-cultured in conditioned medium. Our study highlights the critical role of microglia in type I interferon responses in PD. Additionally, we identified transcription factors NFATc2 as key regulators of aberrant type I interferon responses and microglial pro-inflammatory activation in PD. These findings provide new insights into the pathogenesis of PD and may have implications for the development of novel therapeutic strategies.

Abstract This study aimed to develop and validate a deep learning radiomics nomogram (DLRN) for the preoperative evaluation of axillary lymph node (ALN) metastasis status in patients with a newly diagnosed unifocal breast cancer. A total of 883 eligible patients with breast cancer who underwent preoperative breast and axillary ultrasound were retrospectively enrolled between April 1, 2016, and June 30, 2022. The training cohort comprised 621 patients from Hospital I; the external validation cohorts comprised 112, 87, and 63 patients from Hospitals II, III, and IV, respectively. A DLR signature was created based on the deep learning and handcrafted features, and the DLRN was then developed based on the signature and four independent clinical parameters. The DLRN exhibited good performance, yielding areas under the receiver operating characteristic curve (AUC) of 0.914, 0.929, and 0.952 in the three external validation cohorts, respectively. Decision curve and calibration curve analyses demonstrated the favorable clinical value and calibration of the nomogram. In addition, the DLRN outperformed five experienced radiologists in all cohorts. This has the potential to guide appropriate management of the axilla in patients with breast cancer, including avoiding overtreatment.

Abstract Background The relationship between vitamin D status and mortality among adults with hypertension remains unclear. Methods This prospective cohort study involved a sample of 19,500 adults with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. We utilized a weighted COX proportional hazard model to assess the association between vitamin D status and mortality. This statistical model calculates hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI). Results The study indicated that lower serum 25(OH)D concentration was associated with an increased risk of all-cause mortality among individuals with hypertension. Specially. Those with concentrations between 25.0 and 49.9 nmol/L (HR = 1.71, 95%CI = 1.22–2.40) and less than 25.0 nmol/L (HR = 1.97, 95%CI = 1.15–3.39) had higher hazard ratios for all-cause mortality. Individuals with hypertension who took vitamin D supplements had a lower risk of all-cause mortality, but not the risk of CVD mortality (HR 0.75, 95%CI 0.54–1.03), compared to those who did not supplement (HR = 0.76, 95%CI = 0.61–0.94). Subgroup analysis further revealed that vitamin D supplementation was associated with a reduced risk of all-cause mortality among individuals without diabetes (HR = 0.65, 95%CI = 0.52–0.81) and individuals without CVD (HR = 0.75, 95%CI = 0.58–0.97), and a decreased risk of CVD mortality among individuals without diabetes (HR = 0.63, 95%CI = 0.45–0.88) and without CVD (HR = 0.61, 95%CI = 0.40–0.92). Furthermore, higher-dose vitamin D supplementation was also associated with a greater reduction in all-cause mortality among hypertensive individuals, and there was the potential synergistic effect of combining normal-dose calcium and vitamin D supplementation, showing a superior effect on mortality compared to low-dose supplementation in adults with hypertension. Conclusions This prospective cohort study demonstrated a significant association between lower serum 25 (OH)D concentration and increased all-cause mortality among adults with hypertension. Furthermore, the study found that vitamin D supplementation had a strong and significantly positive correlation with reduced all-cause and CVD mortality among hypertensive individuals without diabetes or CVD. This positive correlation suggests that vitamin D supplementation could potentially be an effective strategy to reduce the risk of mortality in this specific group of people.

The role of co-agonists of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) in chronic kidney disease (CKD) remains unclear. Herein we found that GLP-1R and GCGR expression levels were lower in the kidneys of mice with CKD compared to healthy mice and were correlated with disease severity. Interestingly, GLP-1R or GCGR knockdown aggravated the progression of kidney injury in both diabetic db/db mice and non-diabetic mice undergoing unilateral ureteral obstruction (UUO). Based on the importance of GLP-1R and GCGR in CKD, we reported a novel monomeric peptide, 1907-B, with dual-agonism on both GLP-1R and GCGR. The data confirmed that 1907-B had a longer half-life than long-acting semaglutide in rats or cynomolgus monkeys (∼2–3 fold) and exhibited better therapeutic contribution to CKD than best-in-class monoagonists, semaglutide, or glucagon, in db/db mice and UUO mice. Various lock-of-function models, including selective pharmacological activation and genetic knockdown, confirmed that 1907-B's effects on ameliorating diabetic nephropathy in db/db mice, as well as inhibiting kidney fibrosis in UUO mice, were mediated through GLP-1 and glucagon signaling. These findings highlight that 1907-B, a novel GLP-1R and GCGR co-agonist, exerts multifactorial improvement in kidney injuries and is an effective and promising therapeutic option for CKD treatment.

Abstract In this study, a new short‐term wind power prediction model based on a temporal convolutional network (TCN) and the Informer model is proposed to solve the problem of low prediction accuracy caused by large wind speed fluctuations in short‐term prediction. First, an input feature selection method based on the maximum information coefficient is proposed after considering the problem of information interference caused by excessively large input features. A dynamic time planning method is used to select the optimal input step of historical power. Then, the combined forecasting model composed of TCN and the Informer is constructed in accordance with the numerical weather forecast and historical power data. Lastly, the pinball loss function is used to expand the prediction model into a quantile regression model, measure the effect of volatility, quantify the volatility range of prediction, and finally, obtain a deterministic prediction result. The actual measured data of wind farms in the Bohai Sea area are selected for analysis and calculation. The results show that the prediction model proposed in this study achieves better accuracy in deterministic prediction and interval prediction than the traditional model.

DSN1 has been previously found to be positively correlated with various cancers. However, the effect of DSN1 or its methylation on the prognosis, molecular characteristics, and immune cell infiltration of low-grade glioma (LGG) has not yet been studied. We obtained 1046 LGG samples from the The Cancer Genome Atlas, The Chinese Glioma Genome Atlas (CGGA) microarray, and CGGA RNA-Seq databases. Bioinformatic methods (gene set enrichment analysis (GSEA), chi-square test, multivariate), and laboratory validation were used to investigate DSN1 in LGG. The expression levels of DSN1 mRNA and protein in LGG were substantially higher than those in normal brain tissue, and their expression was negatively regulated by methylation. The survival time of patients with low expression of DSN1 and cg12601032 hypermethylation was considerably prolonged. DSN1 was a risk factor, and of good diagnostic and prognostic value for LGG. Importantly, the expression of DSN1 is related to many types of tumor-infiltrating immune cells and has a positive correlation with PDL1. DSN1 promoted the activation of multiple cancer-related pathways, such as the cell cycle. Additionally, knockdown of DSN1 substantially inhibited the proliferation and invasion of LGG cells. To the best of our knowledge, this study is the first comprehensive analysis of the mechanism of DSN1 leading to poor prognosis of LGG, which provides a new perspective for revealing the pathogenesis of LGG. DSN1 or its methylation has diagnostic value for the prognosis of glioma, and may become a new biological target of anti-tumor immunotherapy.

ABSTRACTAn early and accurate diagnosis of septic cardiomyopathy is vital for improving the overall prognosis of sepsis. In our research, we aimed to identify signature genes and their immune connections in septic cardiomyopathy. By analyzing the mouse myocardial transcriptome from sepsis induced by cecum ligation and puncture (CLP), we identified four distinct k-means clusters. Further analysis of human myocardial datasets using Weighted Gene Co-expression Network Analysis (WGCNA) revealed a strong correlation between the MEturquoise module and septic cardiomyopathy (cor = 0.79, p